Validation of therapeutic approaches targeting epigenetic enzymes in a pre-clinical model of congenital myopathies.

Skeletal muscle contraction starts when Ca2+ is released from the sarcoplasmic reticulum via the ryanodine receptor (RyR1). Defects in Ca2+ signaling, often due to RYR1 mutations, cause neuromuscular disorders like malignant hyperthermia and congenital myopathies. To study recessive RYR1 mutations, a mouse model (dHT) was created with specific mutations found in a child with multi-minicore disease (MmD). Treatment of dHT mice with drugs targeting epigenetic enzymes (HDACs and DNMT inhibitors) improved muscle strength and function. The study aims to explore the biochemical changes these drugs trigger, potentially leading to clinical trials for treating congenital myopathies.